Both human and murine lymphomas apparently reflect neoplastic transformation occurring in either the B-cell or T-cell lineage of the immune system. The pathologic process (or processes) involved in this transformation is unclear, but probably represents either an intrinsic B-cell or T-cell defect or an alteration in immunoregulatory cells. In SJL/J mice as in man, most lymphomas apparently arise in the B-cell system. The SJL/J model lymphoma appears to evolve through a specific form of atypical lymphoid hyperplasia similar to that often seen in human patients which eventuates in large cell ("histiocytic" or "immunoblastic") lymphoma - a tumor strikingly similar to the SJL/J lymphoma. We will examine the B-cell system of SJL/J mice in the presumably preneoplastic stages of the disease to ascertain whether aberrant patterns of response to B-cell mitogens and certain types of antigens can be defined. The spontaneous tumors will be characterized for immunologic and gentic membrane markers, cytogenetics, and ultrastructure; these tumors will also be compared with two induced "variants" which appear to be models of graft rejection and dilantin-associated human lymphomas. Tumor stem cells will be assayed and compared in the three model lymphomas as well as in vitro culture to ascertain if the characteristics of the cell renewal source and the phenotypic expression of membrane markers differ in these tumors. Finally, the role of immunosuppression will be studied to determine its effect on lymphomagenesis in these models.